Analysis of Near Full-Length Genomic Sequences of Drug-Resistant HIV-1 Spreading among Therapy-Naïve Individuals in Nagoya, Japan: Amino Acid Mutations Associated with Viral Replication Activity

摘要

We analyzed a total of 12 near full-length genomes of drug-resistant HIV-1 spreading among therapy-naïve individuals in Nagoya, Japan. Genomes comprised seven protease inhibitor (PI)-resistant viruses possessing an M46I (n = 6) or L90M mutation (n = 1) and five non–nucleoside reverse transcriptase inhibitor–resistant viruses possessing a K103N mutation. All 12 viruses conserved both an H87Q mutation in the cyclophilin A–binding site of Gag p24 (capsid) and a T23N mutation in the cysteine-rich domain of Tat protein. PI-resistant viruses commonly possessed two cleavage site mutations in the p6Pol/protease of Pol polyprotein (F48L in p6Pol) and the anchor/core domains of Nef protein (L57V). These amino acid mutations represent candidates for enhancing replication activity of drug-resistant viruses and supporting expansion of such viruses in therapy-naïve individuals.